tbuckley/cabot-search huggingface dataset:
Advancing Health Equity in Cancer-Related Distress: Lessons Learned From the COVID-19 Pandemic on Leveraging Digital Tools and Future Directions
Authors: Derek Falk, Bradley J. Zebrack
Journal: Journal of the National Comprehensive Cancer Network (2022)

"Advancing Health Equity in Cancer-Related Distress: Lessons Learned From the COVID-19 Pandemic on Leveraging Digital Tools and Future Directions" published on Jul 2022 by National Comprehensive Cancer Network.
Integrating Immunotherapy in Early-Stage Triple-Negative Breast Cancer: Practical Evidence-Based Considerations
Authors: Cesar A. Santa-Maria, Maureen O’Donnell, Raquel Nunes, Jean L. Wright, Vered Stearns
Journal: Journal of the National Comprehensive Cancer Network (2022)

The KEYNOTE-522 study is a practice-changing phase III randomized study that demonstrated that the addition of pembrolizumab to polychemotherapy improves outcomes in patients with high-risk early-stage triple-negative breast cancer (TNBC). This regimen is highly efficacious with unprecedented pathologic complete response (pCR) rates, and clinically meaningful improvements in event-free survival (EFS). However, the combination is also associated with significant high-grade treatment-related toxicity. The backbone regimen deviated from common practice, including the addition of carboplatin, lack of dose dense anthracyclines, and adjuvant capecitabine for residual disease, thus brining important questions regarding real-world translation of these results. This brief report practically addresses some of the most relevant questions physicians and patients face in optimizing care using the best available evidence.
Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): an open-label, phase 2 study
Authors: Alison Sehgal, Daanish Hoda, Peter A Riedell, Nilanjan Ghosh, Mehdi Hamadani, Gerhard C Hildebrandt, John E Godwin, Patrick M Reagan, Nina Wagner-Johnston, James Essell, Rajneesh Nath, Scott R Solomon, Rebecca Champion, Edward Licitra, Suzanne Fanning, Neel Gupta, Ronald Dubowy, Aleco D'Andrea, Lei Wang, Ken Ogasawara, Jerill Thorpe, Leo I Gordon
Journal: The Lancet Oncology (2022)
Dendritic cell-mediated cross presentation of tumor-derived peptides is biased against plasma membrane proteins
Authors: Tim B Fessenden, Lauren E Stopfer, Fiona Chatterjee, Julian Zulueta, Josh Mesfin, Therese Cordero Dumit, Irene Reijers, Esmee P Hoefsmit, Christian Blank, Forest White, Stefani Spranger
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background For effective tumor elimination, cytotoxic CD8 + T cells must recognize tumor-derived antigens presented on class I major histocompatibility complex (MHC-I). Despite a general association between the expression of immunogenic antigens, typically neoantigens, and response to immunotherapy, the majority of patients lack strong endogenous responses to most putative neoantigens due to mechanisms that are not well understood. Cytotoxic CD8 + T-cell responses are induced by dendritic cells (DCs) cross-presenting tumor-derived peptides on MHC-I. We hypothesized that cross presentation may form an unappreciated source of bias in the induction of cytotoxic T-cell responses. Methods We used stable isotope labeling of amino acids combined with immunopeptidomics to distinguish cross-presented from endogenous MHC-I peptides on DCs. To test impacts on T-cell activation, we targeted the model antigen SIINFEKL to specific subcellular compartments in tumor cells, which were used as sources for cross presentation to T cells. In vitro observations were validated using DNA and RNA sequencing data from two cohorts of patients with melanoma undergoing checkpoint blockade therapy. We used a novel quantitative mass spectrometry approach to measure the levels of model antigen on cross-presenting DCs following various means of tumor cell death. Results DCs exhibited a strong bias for cross-presenting peptides derived from cytoplasmic proteins and against those from plasma membrane proteins, which was confirmed using the model antigen SIINFEKL. In patients with melanoma, the proportion of membrane-derived neoantigens was correlated with reduced survival and failure to respond to therapy. Quantification of cross-presented SIINFEKL revealed that the mode of cell death could overcome DCs’ bias against plasma membrane proteins. Conclusions Cross presentation of cellular antigens by DCs may impose constraints on the range of peptides available to activate CD8 + T cells that have previously gone unappreciated. The share of neoantigens arising from membrane-derived sources may render some tumors less immunogenic due to inefficient cross presentation. These observations carry important implications for the encounter and intracellular processing of cellular antigens by DCs and merit further clinical studies for their therapeutic potential in stratifying patient populations and design of vaccine-based therapies.
Online Pharmacy Accessibility of Imatinib, An Oral Chemotherapy Medication
Authors: Yujiao Sun, Adam Hendrix, Benyam Muluneh, Sachiko Ozawa
Journal: Journal of the National Comprehensive Cancer Network (2022)

Background: Since prices of imatinib (Gleevec) remain high, patients on oral chemotherapy are looking for alternative methods to access this life-saving medication. We assessed the accessibility of imatinib through online pharmacies and analyzed each website for medication safety, price, and marketing tactics. Methods: We searched the term “buy imatinib online” using 4 commonly used internet search engines (Google, Bing, Yahoo!, and DuckDuckGo) and screened web pages displayed in the first 10 pages. Websites were included if they were published in English, sold imatinib, were free to access, and offered shipping in the United States. Websites were classified using LegitScript’s categorization as “certified,” “unclassified,” “unapproved,” or “rogue.” We analyzed information on websites’ patient safety characteristics, marketing techniques, pricing, domain registration information, and IP addresses. Results: Of the 44 online pharmacies identified, only 3 (7%) were certified, and the remainder were classified as rogue (52%; n=23), unapproved (30%; n=13), or unclassified (11%; n=5). Thirteen online pharmacies (30%; 9 rogue, 4 unclassified) sold imatinib without a prescription. Nearly one-quarter (n=10) of online pharmacies selling imatinib did not include drug-related warnings on their websites, and nearly half (n=21) did not limit the purchasable quantity. More than three-quarters (n=34) of online pharmacies selling imatinib did not offer pharmacist consultations, even though nearly all websites extended offers to speak with sales associates (91%; n=40). Most online pharmacies selling imatinib claimed price discounts (95%; n=42), but fewer provided bulk discounts (23%; n=10) or coupons (34%; n=15). One-third of rogue pharmacies selling imatinib (n=7) claimed to be registered or accredited on their websites. Conclusions: The lack of safety measures taken by illegitimate online pharmacies endangers patient safety because they allow patients to purchase imatinib without appropriate evaluation for response, drug interactions, and adverse effects. Healthcare providers need to be aware of this practice and should assure patient access to imatinib through safe and legitimate pharmacies.
LMISA: A lightweight multi-modality image segmentation network via domain adaptation using gradient magnitude and shape constraint
Authors: Mina Jafari, Susan Francis, Jonathan M. Garibaldi, Xin Chen
Journal: Medical Image Analysis (2022)

In medical image segmentation, supervised machine learning models trained using one image modality (e.g. computed tomography (CT)) are often prone to failure when applied to another image modality (e.g. magnetic resonance imaging (MRI)) even for the same organ. This is due to the significant intensity variations of different image modalities. In this paper, we propose a novel end-to-end deep neural network to achieve multi-modality image segmentation, where image labels of only one modality (source domain) are available for model training and the image labels for the other modality (target domain) are not available. In our method, a multi-resolution locally normalized gradient magnitude approach is firstly applied to images of both domains for minimizing the intensity discrepancy. Subsequently, a dual task encoder-decoder network including image segmentation and reconstruction is utilized to effectively adapt a segmentation network to the unlabeled target domain. Additionally, a shape constraint is imposed by leveraging adversarial learning. Finally, images from the target domain are segmented, as the network learns a consistent latent feature representation with shape awareness from both domains. We implement both 2D and 3D versions of our method, in which we evaluate CT and MRI images for kidney and cardiac tissue segmentation. For kidney, a public CT dataset (KiTS19, MICCAI 2019) and a local MRI dataset were utilized. The cardiac dataset was from the Multi-Modality Whole Heart Segmentation (MMWHS) challenge 2017. Experimental results reveal that our proposed method achieves significantly higher performance with a much lower model complexity in comparison with other state-of-the-art methods. More importantly, our method is also capable of producing superior segmentation results than other methods for images of an unseen target domain without model retraining. The code is available at GitHub (https://github.com/MinaJf/LMISA) to encourage method comparison and further research.
A retrospective analysis of patients administered neoadjuvant chemotherapy (NACT) with paclitaxel plus carboplatin with oral metronomic chemotherapy (OMCT) in locally advanced borderline resectable/technically unresectable head and neck cancers.
Authors: Shruti Pathak, Zoya Peelay, Vijay Maruti Patil, Vanita Noronha, Nandini Sharrel Menon, Pankaj Chaturvedi, Kumar Prabhash
Journal: Journal of Clinical Oncology (2022)

6030 Background: Neoadjuvant chemotherapy with TPF though the standard is seldom used in India due to its adverse events rate. Two drug regimen of Paclitaxel and Carboplatin (PC) though favoured has inferior outcomes. Hence, we did an analysis to estimate the efficacy and adverse event rate of addition of 3 drug metronomic schedule to PC. Methods: Patients of locally advanced head and neck cancer referred from multidisciplinary board for neoadjuvant chemotherapy and unsuitable for TPF were selected for this analysis. These patients had received 2 drug regimen of intravenous PC with 3 drug regimen of weekly methotrexate 9 mg per m2, Celecoxib 200 mg twice daily, erlotinib 150 mg once daily all administered orally. All patients underwent a response assessment at 5-7 weeks post start of therapy and we're discussed in MDT for further treatment. Adverse events were recorded in accordance with CTCAE version 4.03 and response in accordance with RECIST version 1.1. PFS and OS were estimated with Kaplan Meier method. Results: 72 patients were identified with the median age being 45 (27-80) and M:F ratio (67:5). The indication for NACT were borderline resectability in all patients.. The response rate was 61.1% and grade 3 and above adverse event rate was 33.5%. A total number of 34 among 40 borderline resectable patients underwent surgery. The overall estimated PFS and OS were 18.5 (95%CI = 14.4-22.7) months and 18.05 (95%CI = 14.2-21.8) months respectively. The three most adverse events observed were grade 3 thrombocytopenia in 2 patients (2.8%), grade 3 aspartate aminotransferase (AST) derangement in 4 patients (5.6%) and grade 3 alanine aminotransferase (ALT) in 4 patients (5.6%). Conclusions: The 5 drug combination regimen is safe, tolerable and seems to have similar efficacy as a three drug TPF regimen.
H3K27 acetylation activated-COL6A1 promotes osteosarcoma lung metastasis by repressing STAT1 and activating pulmonary cancer-associated fibroblasts: Erratum
Authors: Ying Zhang, Zhaoyong Liu, Xia Yang, Weiqing Lu, Yelong Chen, Youbin Lin, Jin Wang, Suxia Lin, Jing-Ping Yun
Journal: Theranostics (2022)

[This corrects the article DOI: 10.7150/thno.51245.].
DCLK1 promotes colorectal cancer stemness and aggressiveness via the XRCC5/COX2 axis
Authors: Jee-Heun Kim, So-Yeon Park, So-El Jeon, Jang-Hyun Choi, Choong-Jae Lee, Tae-Young Jang, Hyeon-Ji Yun, Yuno Lee, Pilho Kim, Sang Hee Cho, Ji Shin Lee, Jeong-Seok Nam
Journal: Theranostics (2022)

Rationale: Doublecortin-like kinase 1 (DCLK1) is a serine/threonine kinase that selectively marks cancer stem-like cells (CSCs) and promotes malignant progression in colorectal cancer (CRC). However, the exact molecular mechanism by which DCLK1 drives the aggressive phenotype of cancer cells is incompletely determined. Methods: Here, we performed comprehensive genomics and proteomics analyses to identify binding proteins of DCLK1 and discovered X-ray repair cross-complementing 5 (XRCC5). Thus, we explored the biological role and downstream events of the DCLK1/XRCC5 axis in human CRC cells and CRC mouse models. Results: The results of comprehensive bioinformatics analyses suggested that DCLK1-driven CRC aggressiveness is linked to inflammation. Mechanistically, DCLK1 bound and phosphorylated XRCC5, which in turn transcriptionally activated cyclooxygenase-2 expression and enhanced prostaglandin E2 production; these events collectively generated the inflammatory tumor microenvironment and enhanced the aggressive behavior of CRC cells. Consistent with the discovered mechanism, inhibition of DCLK1 kinase activity strongly impaired the tumor seeding and growth capabilities in CRC mouse models. Conclusion: Our study illuminates a novel mechanism that mediates the pro-inflammatory function of CSCs in driving the aggressive phenotype of CRC, broadening the biological function of DCLK1 in CRC.
Loss of MLKL ameliorates liver fibrosis by inhibiting hepatocyte necroptosis and hepatic stellate cell activation
Authors: Ren Guo, Xiaohui Jia, Zhenbin Ding, Gang Wang, Mengmeng Jiang, Bing Li, Shanshan Chen, Bingqing Xia, Qing Zhang, Jian Liu, Ruting Zheng, Zhaobing Gao, Xin Xie
Journal: Theranostics (2022)

Background: Liver fibrosis affects millions of people worldwide without an effective treatment.Although multiple cell types in the liver contribute to the fibrogenic process, hepatocyte death is considered to be the trigger.Multiple forms of cell death, including necrosis, apoptosis, and necroptosis, have been reported to co-exist in liver diseases.Mixed lineage kinase domain-like protein (MLKL) is the terminal effector in necroptosis pathway.Although necroptosis has been reported to play an important role in a number of liver diseases, the function of MLKL in liver fibrosis has yet to be unraveled.Methods and Results: Here we report that MLKL level is positively correlated with a number of fibrotic markers in liver samples from both patients with liver fibrosis and animal models.Mlkl deletion in mice significantly reduces clinical symptoms of CCl4-and bile duct ligation (BDL) -induced liver injury and fibrosis.Further studies indicate that Mlkl -/-blocks liver fibrosis by reducing hepatocyte necroptosis and hepatic stellate cell (HSC) activation.AAV8-mediated specific knockdown of Mlkl in hepatocytes remarkably alleviates CCl4-induced liver fibrosis in both preventative and therapeutic ways.Conclusion: Our results show that MLKL-mediated signaling plays an important role in liver damage and fibrosis, and targeting MLKL might be an effective way to treat liver fibrosis.
Blockade of phosphotyrosine pathways suggesting SH2 superbinder as a novel therapy for pulmonary fibrosis
Authors: Meng Wang, An-Dong Liu, Qian Niu, Xiao Feng, Yuan-Yi Zheng, Shuai-Jun Chen, Hui Xu, Qian Li, Guo-Qing Hou, Xiao-Yang Bi, Yu-Zhi Lu, Pei-Pei Cheng, Li-Mei Liang, Ye-Han Jiang, Li-Qin Zhao, Fei Liu, Lin-Jie Song, Li-Ling Zhou, Ling-Yan Xiao, Feng Chen, Shawn Shun-Cheng Li, Wan-Li Ma, Xuan Cao, Hong Ye
Journal: Theranostics (2022)

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible fibrotic disease with high mortality.Currently, pirfenidone and nintedanib are the only approved drugs for IPF by the U.S. Food and Drug Administration (FDA), but their efficacy is limited.The activation of multiple phosphotyrosine (pY) mediated signaling pathways underlying the pathological mechanism of IPF has been explored.A Src homology-2 (SH2) superbinder, which contains mutations of three amino acids (AAs) of natural SH2 domain has been shown to be able to block phosphotyrosine (pY) pathway.Therefore, we aimed to introduce SH2 superbinder into the treatment of IPF.Methods: We analyzed the database of IPF patients and examined pY levels in lung tissues from IPF patients.In primary lung fibroblasts obtained from IPF patient as well as bleomycin (BLM) treated mice, the cell proliferation, migration and differentiation associated with pY were investigated and the anti-fibrotic effect of SH2 superbinder was also tested.In vivo, we further verified the safety and effectiveness of SH2 superbinder in multiple BLM mice models.We also compared the anti-fibrotic effect and side-effect of SH2 superbinder and nintedanib in vivo.Results: The data showed that the cytokines and growth factors pathways which directly correlated to pY levels were significantly enriched in IPF.High pY levels were found to induce abnormal proliferation, migration and differentiation of lung fibroblasts.SH2 superbinder blocked pY-mediated signaling pathways and suppress pulmonary fibrosis by targeting high pY levels in fibroblasts.SH2 superbinder had better therapeutic effect and less side-effect compare to nintedanib in vivo.Conclusions: SH2 superbinder had significant anti-fibrotic effects both in vitro and in vivo, which could be used as a promising therapy for IPF.
Injectable electrospun fiber-hydrogel composite sequentially releasing clonidine and ropivacaine for prolonged and walking regional analgesia
Authors: Sufang Chen, Weifeng Yao, Haixia Wang, Tienan Wang, Xue Xiao, Guoliang Sun, Jing Yang, Yu Guan, Zhen Zhang, Zhengyuan Xia, Mingqiang Li, Yu Tao, Ziqing Hei
Journal: Theranostics (2022)

Rationale: Peripheral nerve block is a traditional perioperative analgesic method for its precise pain control and low systemic toxicity.However, a single low dose of local anesthetic merely provides a few hours of analgesia, and high dose results in irreversible toxicity, whereas continuous infusion of anesthetics is expensive and complicated.Therefore, it is necessary to develop a long-acting and sensory-selective local anesthetic for safe perioperative analgesia.Methods: An injectable composite comprising ropivacaine-loaded poly (ε-caprolactone) electrospun fiber and clonidine-loaded F127 hydrogel (Fiber-Rop/Gel-Clo composite) was developed for long-acting and walking regional analgesia with barely one dose.The peripheral nerve blockade effect of the composite was evaluated in a rat sciatic nerve block model.Also, the biodegradability and biosafety of the composite was evaluated.Results: The preferentially released Clo from the hydrogel rapidly constricted the peripheral arterial vessels, reducing the blood absorption of Rop and thus enhancing the local Rop accumulation at the injection site.The subsequently sustainable release of Rop from the fiber, significantly prolonged the sciatic nerve block of rats.Remarkably, an amazing sensorimotor segregation effect was achieved, as the sensory blockade (32.0 ± 1.4 h) lasted significantly longer than the motor blockade (20.3 ± 0.9 h).Additionally, the Fiber-Rop/Gel-Clo composite presented good biodegradability and biosafety in vivo.Conclusions: Our designed Fiber-Rop/Gel-Clo composite with minimal invasion, prolonged synergistic analgesia, and strikingly sensorimotor segregation effect, posted a promising prospect for regional long-term walking analgesia in clinical treatment.
How to improve photodynamic therapy-induced antitumor immunity for cancer treatment?
Authors: Min Zhang, Yifan Zhao, He Ma, Yusong Sun, Jie Cao
Journal: Theranostics (2022)

Photodynamic therapy (PDT) is a promising method of tumor ablation and function-preserving oncological intervention, which is minimally invasive, repeatable, and has excellent function and cosmetic effect, with no cumulative toxicity.More importantly, PDT can induce immunogenic cell death and local inflammation, thus stimulating the body's immune response.However, the weak immunity induced by PDT alone is insufficient to trigger a systemic immune response towards cancer cells.To overcome this obstacle, multiple strategies have been investigated, including tumor microenvironment remodeling, tumor vaccines, subcellular-targeted PDT, and synergistic therapies.This review summarizes the latest progress in the development of strategies to improve the PDT-induced immune effect for enhanced cancer treatment.
Microenvironment Activatable Nanoprodrug Based on Gripper-like Cyclic Phenylboronic Acid to Precisely and Effectively Alleviate Drug-induced Hepatitis: Erratum
Authors: Qixiong Zhang, Shanshan Li, Lulu Cai, Yuxuan Zhu, Xingmei Duan, Peidu Jiang, Lei Zhong, Kun Guo, Rongsheng Tong
Journal: Theranostics (2022)

[This corrects the article DOI: 10.7150/thno.61214.].
Extracellular vesicle-derived miR-144 as a novel mechanism for chronic intermittent hypoxia-induced endothelial dysfunction
Authors: Huina Zhang, Lu Peng, Yifan Wang, Wen Zhao, Wayne Bond Lau, Yajing Wang, Yu Li, Yunhui Du, Linyi Li, Yu Huang, Shaoping Nie, Yanwen Qin, Xinliang Ma, Yongxiang Wei
Journal: Theranostics (2022)

Rationale: Extracellular vesicles (EVs) play a significant role in cell-cell communication.However, whether and how extracellular vesicles are involved in chronic intermittent hypoxia-induced endothelial dysfunction is unknown. Methods:Comparative transcriptomics analysis and miRNA screening were used to identify the possible pathways or target molecules mediating chronic intermittent hypoxia-induced endothelial function.Serum-or erythrocyte-derived EVs were isolated through ultracentrifugation plus filtration.After in vitro or in vivo treatment with EVs, aortic rings were treated with dihydroethidium staining for superoxidative anion measurement or mounted with wire myography to measure isometric forces.Immunoblotting and qPCR were used for evaluating the molecular mechanism mediating EV miR-144-induced endothelial function under intermittent hypoxia. Results:We revealed a previously undefined importance of circulating extracellular vesicles in regulating endothelial function via delivery of miR-144 to endothelial cells, reducing nuclear factor erythroid 2-related factor 2 expression.Additionally, we identified that erythrocytes were the primary cellular source of miR-144-enriched serum-derived extracellular vesicles and that erythrocyte-derived extracellular vesicles were largely responsible for chronic intermittent hypoxia-impaired endothelial function.Furthermore, silencing of miR-144 by anti-miR-144 confirmed its essential role in endothelial dysfunction elicited by erythrocyte-derived extracellular vesicles from chronic intermittent hypoxia-exposed C57BL/6 mice. Conclusion:The results expand the scope of blood-borne substances involved in vascular homeostasis and suggest that anti-miR-144-loaded extracellular vesicles may represent a promising therapeutic approach against obstructive sleep apnea or chronic intermittent hypoxia-associated endothelial dysfunction.